Ann Rheum Dis: first published as 10.1136/annrheumdis-2018-214644 on 13 February 2019. Downloaded from Myositis

Clinical science [18F] positron emission tomography: identification of muscle amyloid in inclusion body myositis and differentiation from polymyositis James B Lilleker,‍ ‍ 1,2 Richard Hodgson,3,4 Mark Roberts,2 Karl Herholz,5 James Howard,3 Rainer Hinz,5 Hector Chinoy‍ ‍ 4,6

Handling editor Josef S Abstract Key messages Smolen Objectives With the tools available currently, confirming the diagnosis of inclusion body myositis (IBM) ►► Additional material is What is already known about this subject? published online only. To view can be difficult. Many patients are initially misdiagnosed ►► Positron emission tomography can detect please visit the journal online with polymyositis (PM). In this observational study tissue deposits of amyloid, potentially allowing (http://dx.​ ​doi.org/​ ​10.1136/​ ​ at a UK adult neuromuscular centre, we investigated non-invasive differentiation of inclusion body annrheumdis-2018-​ ​214644). whether amyloid positron emission tomography could myositis (IBM) from polymyositis (PM). For numbered affiliations see differentiate between IBM and PM. Methods Ten patients with IBM and six with PM end of article. What does this study add? underwent clinical review, [18F]florbetapir positron ►► Significantly increased intramuscular amyloid Correspondence to emission tomography and MRI of skeletal musculature. levels were found in IBM. Dr James B Lilleker, Centre Differences in [18F]florbetapir standardised uptake ► Amyloid levels generally correlated poorly with for Musculoskeletal Research, value ratios in skeletal muscle regions of interest were ► Stopford Building, Oxford Road, disease severity, muscle and fatty evaluated. Relationships between [18F]florbetapir The University of Manchester, infiltration levels. Manchester, UK; standardised uptake value ratios and measures of james.​ ​lilleker@manchester.​ ​ac.uk​ disease severity (clinical and by MRI of skeletal muscle) How might this impact on clinical practice or were assessed. RH and HC contributed equally. future developments? Results [18F]florbetapir standardised uptake value ► Muscle amyloid imaging can differentiate ratios were significantly higher in those withI BM ► Received 25 October 2018 between IBM and PM and could prove a useful Revised 6 December 2018 compared with PM for all assessed regions (total-[18F] future diagnostic modality. Accepted 29 December 2018 florbetapir standardised uptake value ratio 1.45 (1.28 Published Online First to 2.05) vs 1.01 (0.80 to 1.22), p=0.005). For total- 13 February 2019 [18F]florbetapir standardised uptake value ratios≥1.28, sensitivity has been demonstrated, particularly sensitivity and specificity forI BM was 80% and 100%, in early IBM.5 Recent diagnostic criteria for IBM respectively. have shifted towards identification of the charac-

Conclusions [18F]florbetapir amyloid positron emission http://ard.bmj.com/ teristic pattern of muscle weakness, with less strict tomography differentiates IBM from PM. Successful histopathological requirements.4 While this has development could facilitate accurate diagnosis, inclusion improved sensitivity, clinically detectable weak- in clinical trials and help avoid unnecessary exposure to ness implies that significant and irreversible muscle potentially harmful treatments. damage has occurred, reducing the likelihood that novel treatments will be effective. We hypothesise that using amyloid positron emis- on September 29, 2021 by guest. Protected copyright. Introduction sion tomography (amyloid-PET) to detect beta-am- Inclusion body myositis (IBM) is an acquired yloid within muscle can distinguish IBM from other muscle disease with a slowly progressive course, inflammatory myopathies. Unlike muscle , culminating in severe disability.1 IBM is catego- imaging is non-invasive and large volumes of muscle rised as an inflammatory myopathy and shares can be studied, potentially improving sensitivity and histopathological features with polymyositis (PM), facilitating earlier diagnosis. In this imaging study but immunosuppression does not modify progres- we compared the intramuscular amyloid burden, as sion.2 IBM is often diagnosed late and is commonly determined using amyloid-PET, between IBM and misdiagnosed initially as PM, due in part because PM. (E)-4-(2-(6-(2-(2-(2-18F-fluoroethoxy)ethoxy) differentiation on histopathological grounds can ethoxy)pyridin-3-yl)vinyl)-N-methyl benzenamine, be difficult. In one study, five of nine patients with here referred to as [18F]florbetapir, was used as the amyloid imaging agent.6 7 © Author(s) (or their a diagnosis of ‘PM’ developed clinical features of employer(s)) 2019. Re-use IBM during follow-up, with such patients receiving permitted under CC BY. unnecessary and potentially harmful immunosup- Methods Published by BMJ. pressive treatments.3 Participants To cite: Lilleker JB, The presence of intramuscular beta-amyloid Between October 2015 and October 2016, written Hodgson R, Roberts M, forms part of several IBM diagnostic criteria and informed consent was provided by 10 cases with et al. Ann Rheum Dis is a key difference from PM.4 While this feature IBM and 6 with PM selected from the database of 2019;78:657–662. has a high diagnostic specificity, a relatively low patients attending the adult neuromuscular service

Lilleker JB, et al. Ann Rheum Dis 2019;78:657–662. doi:10.1136/annrheumdis-2018-214644 657 Ann Rheum Dis: first published as 10.1136/annrheumdis-2018-214644 on 13 February 2019. Downloaded from Myositis at Salford Royal NHS Foundation Trust, UK. For the PM cohort, For correction of non-specific radiotracer binding, a reference we restricted recruitment to those aged >45 years (online region was defined within the lumbar fat pad using the same supplementary appendix section 3). IBM cases met European centre landmark as the forearm ROI. Standardised [18F]flor- Neuromuscular Centre 2011 diagnostic criteria (‘clinicopatho- betapir uptake values (SUVs) were calculated for each ROI by logically defined’ (n=8) or ‘clinically defined’ (n=2)).8 Those dividing the decay-corrected tissue mean concentration of radio- with PM met Bohan and Peter diagnostic criteria (probable or activity by the total injected radioactivity per body weight. Sum definite) and had a minimum classification probability of 75% intensity means for all regions, upper limb regions and lower using the International Myositis Classification Criteria Project limb regions were calculated. SUV ratios (SUVRs) were calcu- criteria.9–11 lated using the lumbar fat pad reference. This region was chosen as large volumes were available for selection and the location was easily matched between participants. Cerebral amyloid imaging Study procedures studies have also shown increased statistical power when using Clinical outcomes lipid-rich reference regions.17 Given the lipophilic nature of flor- For those with IBM the Functional Rating Scale (IBM-FRS) was betapir, it was assumed that tracer binding in the subcutaneous performed.12 In PM, the International Myositis Assessment & adipose was predominantly of the non-specific type. Clinical Studies Group disease activity core set measures were completed.13 Both groups had muscle strength assessed using the manual muscle testing 260 (MMT26) score and completed the MRI Health Assessment Questionnaire disability index (HAQ-DI).14 Images were scored by a blinded musculoskeletal radiologist (JH) using semiquantitative scoring tools based on those in the liter- ature.18–20 Severity of fatty infiltration (0: normal, 5: end-stage PET appearance) and extent of inflammatory change (0: normal, A target dose of 370 MBq (18F)florbetapir was administered 5: entire muscle) were scored (online supplementary appendix by intravenous bolus. A CT scan from shoulders to ankles was section 2). For comparison with the amyloid-PET, mean fatty performed using a Siemens Biograph TruePoint PET/CT camera infiltration and inflammation scores for corresponding muscle for attenuation correction and definition of regions of interest regions were calculated. (ROI).15 A PET emission scan of the same area commenced 45 min after radiotracer injection. Five minutes for each of the eight or nine bed positions was used, depending on subject height. Statistical analysis PET images were reconstructed using 3D Ordered Subset [18F]florbetapir SUVs and SUVRs for IBM were compared Expectation Maximisation with three iterations and 21 subsets with PM using the Mann-Whitney Ranksum test in STATA for producing whole body images with almost isotropic voxels Windows V.13.0 (College Station, Texas, USA). For the IBM (2.6728 mm×2.6728 mm×2.027 mm) and a matrix size of group, correlations between [18F]florbetapir SUVRs and clin- 256×256 voxels per transaxial plane. A 3D Gaussian filter (full ical and MRI parameters of disease severity were examined width at half maximum 3 mm) was applied postreconstruction using Spearman’s ranked correlation. Two-sided students t-test to regularise images. or Fisher’s exact test were used where appropriate. Receiver operating characteristic analysis was performed regarding the sensitivity and specificity of the total-[18F]florbetapir SUVRs MRI for IBM. P<0.05 was considered as significant. Disease duration

On the same day, whole body MRI was performed on a Philips http://ard.bmj.com/ refers to the interval between diagnosis and the date of partici- Achieva 1.5 T scanner. A T1-weighted (TR 500 ms, TE 20 ms, pation in the study. bandwidth 220 Hz) sequence (to assess fatty infiltration of muscle) and a short tau inversion recovery (TR 5320 ms, TE 50 ms, TI 150 ms, bandwidth 170 Hz) sequence (to assess myoedema, a Ethical and regulatory approvals surrogate for muscle inflammation) were performed. The study was sponsored by the University of Manchester and authorised by the UK National Research Ethics Service (Greater

Manchester West, 15/NW/0547) and the Administration of on September 29, 2021 by guest. Protected copyright. Image processing Radioactive Substances Advisory Committee (RPC number: PET 595/3586/33509). Seven muscle ROIs were defined for each subject, consisting of all muscle within a 10 cm vertical stack of consecutive images from the anatomical CT scan. The placement of this section was Results centred on a slice 1/3 of the distance from the superior border Thirteen male and three female participants were studied of the patella to the anterior superior iliac spine for the thigh, (table 1). Three of the IBM group had previously received immu- 1/3 of the distance from the inferior border of the patella to the nosuppressant medication, compared with all in the PM group. summit of the medial malleolus for the calf, 1/2 of the distance Visible differences were evident when comparing [18F]flor- from the greater tuberosity of the humerus to the medial epicon- betapir PET/CT images between those with IBM and those with dyle for the left arm and 1/2 of the distance from the tip of the PM (figure 1). [18F]Florbetapir SUVRs were significantly higher olecranon to the ulnar styloid process for the forearm. Each ROI in those with IBM for all ROIs (p value range 0.002–0.030) was constructed using semiautomated threshold active contour (table 1 and figure 2). For [18F]florbetapir SUVs (ie, without segmentation tools within ITK-SNAP (online supplementary adjustment for non-specific radiotracer binding), only trends appendix section 1).16 Intensities of fat and muscle were spec- towards higher values in the IBM group were observed, except ified (muscle: −10 to +100 HU; fat: −150 to −50 HU) and for the total-SUV region, where significantly higher values were seed ‘bubbles’ placed within all visible musculature. Contour also seen (table 1). For a total-[18F]florbetapir SUVR≥1.28 the evolution could iterate until no further expansion of the ROI diagnostic sensitivity for IBM was 80% and specificity 100% occurred. (area under curve 0.93).

658 Lilleker JB, et al. Ann Rheum Dis 2019;78:657–662. doi:10.1136/annrheumdis-2018-214644 Ann Rheum Dis: first published as 10.1136/annrheumdis-2018-214644 on 13 February 2019. Downloaded from Myositis

Table 1 Clinical characteristics of subjects and muscle [18F]florbetapir uptake values IBM PM (n=10) (n=6) P value Mean age in years at diagnosis (SD) 64.3 (8.4) 58.2 (10.7) 0.222* Mean age in years at scan (SD) 68.3 (8.0) 59.7 (11.1) 0.092* Mean disease duration at scan in years (SD) 4.0 (3.0) 1.5 (1.4) 0.079* Gender (Male | Female) 9 | 1 4 | 2 0.036† Mean manual muscle testing score (0–260) (SD) 236 (22.9) 256 (2.3) 0.052* Mean Health Assessment Questionnaire disability index (SD) 1.3 (0.7) 0.8 (0.8) 0.192* Mean IBM-Functional Rating Scale (0–40) (SD) 28.9 (5.3) – – Mean physician global disease activity VAS (0–10) (SD) – 1.8 (1.5) – Mean serum total creatine kinase level (IU/L) (SD) 579 (408)‡ 308 (220) – Current immunosuppressive treatments (n) Nil Prednisolone (5/6) – Methotrexate (2/6) Azathioprine (2/6) Cyclophosphamide (1/6) Previous immunosuppressive treatments (n) Prednisolone (3/10) Cyclophosphamide (2/6) – Azathioprine (1/10) Prednisolone (1/6) Mycophenolate (1/10) Mycophenolate (1/6) Azathioprine (1/6) Ciclosporin (1/6) IVIG (1/6) Median [18F]florbetapir SUV (IQR) Left arm 0.47 0.40 0.104§ (0.41–0.55) (0.36–0.48) Right forearm 0.39 0.32 0.104§ (0.35–0.42) (0.27–0.40) Left forearm 0.45 0.33 0.129§ (0.32–0.55) (0.30–0.36) Right thigh¶ 0.44 0.41 0.288§ (0.43–0.52) (0.37–0.45) Left thigh¶ 0.48 0.41 0.059§ (0.43–0.51) (0.36–0.45) Right calf 0.51 0.46 0.233§ (0.45–0.61) (0.44–0.50) Left calf 0.51 0.43 0.233§ (0.40–0.58) (0.39–0.45) Overall (total-SUV) 0.48 0.42 0.039§ (0.44–0.51) (0.39–0.45)

Median [18F]florbetapir SUVR (IQR) Left arm¶ 1.61 0.96 0.002§ http://ard.bmj.com/ (1.43–1.81) (0.82–1.08) Right forearm 1.26 0.79 0.005§ (1.05–1.60) (0.67–0.91) Left forearm 1.26 0.83 0.005§ (1.12–1.52) (0.58–0.96) Right thigh** 1.34 1.04 0.013§

(1.31–1.77) (0.79–1.21) on September 29, 2021 by guest. Protected copyright. Left thigh** 1.40 0.99 0.005§ (1.40–1.87) (0.79–1.18) Right calf 1.59 1.09 0.013§ (1.36–2.29) (0.94–1.35) Left calf 1.56 1.00 0.030§ (1.29–2.40) (0.75–1.31) Overall (total-SUVR) 1.45 1.01 0.005§ (1.28–2.05) (0.80–1.22) Bold values indicate statistically significant differences. *P values derive from two-sided students t-test. †Fisher’s exact test. ‡For the IBM group, this refers to the peak serum creatine kinase level (it was not rechecked at the time of the scan). §The Mann-Whitney Ranksum test. ¶The right arm was not used because radiotracer administration was via a venous cannula in the right antecubital fossa, except in two subjects (one with PM, one with IBM) where the reverse was true due to difficulties with cannula placement. **n=9 for IBM group. Measurement in one subject could not be obtained due to very high levels of muscle atrophy and fatty replacement. IBM, inclusion body myositis; IVIG, intravenous immunoglobulin; PM, polymyositis; SUV, standardised uptake value; SUVR, standardised uptake value ratio with reference region in lumbar fat pad; VAS, visual analogue scale.

Lilleker JB, et al. Ann Rheum Dis 2019;78:657–662. doi:10.1136/annrheumdis-2018-214644 659 Ann Rheum Dis: first published as 10.1136/annrheumdis-2018-214644 on 13 February 2019. Downloaded from Myositis

Figure 1 (18F)florbetapir PET/CT images showing differences in uptake between a participant with inclusion body myositis (panel A) and one with polymyositis (panel B). Increasing SUVs (red) indicate increased tracer uptake. [18F]Florbetapir PET images overlay spatially aligned CT images. Top of each panel depicts axial and coronal slices though the thigh. Bottom of each panel depicts axial and coronal slices though the calf. Each image is http://ard.bmj.com/ centred on the middle of the defined region of interest. PET, positron emission tomography; SUVs, standardised uptake values.

In those with IBM, only in the calves were strong nega- IBM was high, highlighting the potential diagnostic usefulness tive correlations between [18F]florbetapir SUVRs and muscle of muscle amyloid-PET. Further development of this technique inflammation levels (by MRI) found (right calf Rho −0.73, could facilitate accurate diagnosis of IBM in those with early and p=0.02; left calf Rho −0.68, p=0.03). No significant correla- otherwise undifferentiated disease, avoiding the use of potentially on September 29, 2021 by guest. Protected copyright. tion between [18F]florbetapir SUVRs and levels of fatty infiltra- harmful treatments and facilitating inclusion in clinical trials. tion were identified. Furthermore, no significant relationships To our knowledge, only one other published study used PET between the total-[18F]florbetapir SUVR and the age at scan, to detect intramuscular amyloid in IBM.21 Maetzler et al used disease duration, MMT26, HAQ-DI or IBM-FRS were iden- the Pittsburgh-B (PiB) compound; a carbon-11 based radionucle- tified. This included subsets of the MMT26 and IBM-FRS otide with a half-life of approximately 20 min (compared with restricted to upper limb and lower limb components compared 110 min for fluorine-18), limiting its clinical use. Uniquely, we with corresponding upper limb and lower limb [18F]florbetapir also performed same day muscle MRI and collected standardised SUVRs (online supplementary appendix section 1 table 1) . clinical disease severity measures. Amyloid deposits (by congo red staining) were only found in the We used a semiautomated contour evolution method to diagnostic muscle biopsy of one IBM participant. No differences select large sections of muscle for ROIs.16 It is likely that our in the total-[18F]florbetapir SUVR were found according to method, rather than selecting small ellipsoid regions, produces the presence of degenerative biopsy features, including rimmed more reliable results due to lower susceptibility to noise and bias vacuoles (online supplementary appendix section 1 table 2). from manual ROI placement. Borderline lower [18F]florbetapir SUVRs were found in the forearm when compared with other Discussion regions in both groups, potentially due to increased noise at the In all assessed muscle groups, significantly increased [18F]flor- edge of the field of view. As we performed sequential exposures, betapir SUVRs were evident in IBM compared with PM. Sensi- comparison between different regions is susceptible to error, tivity and specificity of the total-[18F]florbetapir SUVR for even after correction for radioactivity decay.

660 Lilleker JB, et al. Ann Rheum Dis 2019;78:657–662. doi:10.1136/annrheumdis-2018-214644 Ann Rheum Dis: first published as 10.1136/annrheumdis-2018-214644 on 13 February 2019. Downloaded from Myositis

Figure 2 Comparison of SUVRs of [18F]florbetapir between participants ithw IBM (filled circles) and those with PM (open triangles) across seven different muscle regions and a combined region. Thick horizontal lines represent median SUVR and thin horizontal lines indicate the IQR. P values derived from Mann-Whitney Ranksum test. *Statistically significant difference (p<0.05). IBM, inclusion body myositis; PM, polymyositis; SUVR, standardised uptake value ratio.

Our study is small and it is possible that factors other than diag- 6Rheumatology Department, Salford Royal NHS Foundation Trust, Salford, United nosis are confounding the results. A trend towards increased age Kingdom at the time of scan is evident in the IBM group, but no significant Acknowledgements We thank all participants for kindly agreeing to take part in correlations between age and the total-[18F]florbetapir SUVRs this study. were evident (Rho=0.33, p=0.22), indicating that age alone Collaborators Sarah Wood, Peter Julyan, David Ashworth, Gerrit van der Vegte, http://ard.bmj.com/ is unlikely to explain the differences in intramuscular amyloid Mike Godfrey, Eleanor Duncan-Rouse, Barry Whitnall, Amy Watkins, Jonathan Harris, content between the groups. The IBM group also had borderline Mark Guy. lower MMT26 scores. However, total-[18F]florbetapir SUVRs Contributors JBL and HC had the original idea for the project. JBL applied for did not correlate significantly with measures of disease severity funding, obtained ethical approval, designed the study, recruited and assessed subjects, analysed the data and drafted the manuscript. RH assisted with the in this group, including the MMT26. Gender ratios are also design of the study, devised the PET scanning protocol and assisted with analysis different between the groups, but we are not aware of a clear of the data. RH assisted with the design of the study, devised the MRI scanning

rationale as to why this would independently influence the [18F] protocol and assisted with analysis of the data. MER and HC assisted with patient on September 29, 2021 by guest. Protected copyright. florbetapir SUVR. identification and recruitment. KH was theA dministration of Radioactive Substances This study has demonstrated the usefulness of muscle amyloid Advisory Committee (ARSAC) certificate holder. JH assisted with development of the MRI scoring system and scored the MRI scans. All authors contributed to, reviewed imaging using [18F]florbetapir PET in differentiating IBM from and approved the final manuscript. PM. By potentially improving the ability to accurately diagnose Funding This work was supported by a grant from the NIHR Manchester IBM, further development and validation of this technique could Musculoskeletal Biomedical Research Unit (now Biomedical Research Centre), an help to avoid the use of unnecessary medication and enhance award from the Centre for Imaging Sciences at the University of Manchester and involvement in clinical trials. a grant from the Medical Research Council (MR/N003322/1). This report includes independent research supported by the NIHR Biomedical Research Centre Funding Author affiliations Scheme. 1Centre for Musculoskeletal Research, School of Biological Sciences, Faculty of Disclaimer The views expressed in this publication are those of the authors and Biology, Medicine and Health, Manchester Academic Health Science Centre, not necessarily those of the NHS, the National Institute for Health Research or the University of Manchester, Manchester, UK Department of Health. 2Manchester Centre for Clinical Neuroscience, Salford Royal NHS Foundation Trust, Salford, UK Competing interests None declared. 3Radiology Department, Salford Royal NHS Foundation Trust, Salford, United Patient consent for publication Not required. Kingdom Provenance and peer review Not commissioned; externally peer reviewed. 4The National Institute for Health Research Manchester Musculoskeletal Biomedical Research Centre, Manchester University Hospitals NHS FoundationTrust, Manchester Open access This is an open access article distributed in accordance with the Academic Health Science Centre, University of Manchester, Manchester, United Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits Kingdom others to copy, redistribute, remix, transform and build upon this work for any 5Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UK purpose, provided the original work is properly cited, a link to the licence is given,

Lilleker JB, et al. Ann Rheum Dis 2019;78:657–662. doi:10.1136/annrheumdis-2018-214644 661 Ann Rheum Dis: first published as 10.1136/annrheumdis-2018-214644 on 13 February 2019. Downloaded from Myositis and indication of whether changes were made. See: https://​creativecommons.​org/​ 12 Jackson CE, Barohn RJ, Gronseth G, et al. Inclusion body myositis functional rating licenses/by/​ ​4.0/.​ scale: a reliable and valid measure of disease severity. Muscle Nerve 2008;37:473–6. 13 Rider LG, Werth VP, Huber AM, et al. Measures of adult and juvenile dermatomyositis, References polymyositis, and inclusion body myositis: physician and patient/parent global activity, Manual Muscle Testing (MMT), Health Assessment Questionnaire (HAQ)/Childhood 1 Cox FM, Titulaer MJ, Sont JK, et al. A 12-year follow-up in sporadic inclusion body myositis: an end stage with major disabilities. Brain 2011;134:3167–75. Health Assessment Questionnaire (C-HAQ). Arthritis Care Res 2011;63:S118–57. 2 Rose MR, Jones K, Leong K, et al. Treatment for inclusion body myositis. Cochrane 14 Kendall FP, McCreary EK. Muscles, testing and function. Third Edit Williams & Wilkins, database Syst Rev 2015;51. 1983. 3 van der Meulen MF, Bronner IM, Hoogendijk JE, et al. Polymyositis: an overdiagnosed 15 Jakoby BW, Bercier Y, Watson CC, et al. Performance characteristics of a new LSO PET/ entity. Neurology 2003;61:316–21. CT scanner with extended axial Field-of-View and PSF reconstruction. IEEE Trans Nucl 4 lloyd TE, Mammen AL, Amato AA, et al. Evaluation and construction of diagnostic Sci 2009;56:633–9. criteria for inclusion body myositis. Neurology 2014;83:426–33. 16 Yushkevich PA, Piven J, Hazlett HC, et al. User-guided 3D active contour segmentation 5 Brady S, Squier W, Hilton-Jones D. Clinical assessment determines the diagnosis of of anatomical structures: significantly improved efficiency and reliability. Neuroimage inclusion body myositis independently of pathological features. J Neurol Neurosurg 2006;31:1116–28. Psychiatry 2013;84:1240–6. 17 Fleisher AS, Joshi AD, Sundell KL, et al. Use of white matter reference regions for 6 Choi SR, Golding G, Zhuang Z, et al. Preclinical properties of 18F-AV-45: a PET agent detection of change in florbetapir positron emission tomography from completed for Abeta plaques in the brain. J Nucl Med 2009;50:1887–94. phase 3 solanezumab trials. Alzheimer's & 2017;13:1117–24. 7 Wong DF, Rosenberg PB, Zhou Y, et al. In vivo imaging of amyloid deposition in 18 Mercuri E, Talim B, Moghadaszadeh B, et al. Clinical and imaging findings in six cases Alzheimer disease using the radioligand 18F-AV-45 (florbetapir [corrected] F 18). J of congenital muscular dystrophy with rigid spine syndrome linked to chromosome 1p Nucl Med 2010;51:913–20. (RSMD1). Neuromuscul Disord 2002;12:631–8. 8 Rose MR, ENMC IBM Working Group. 188th ENMC International workshop: inclusion 19 Yao L, Gai N. Fat-corrected T2 measurement as a marker of active muscle disease in body myositis, 2-4 December 2011, Naarden, the Netherlands. Neuromuscul Disord inflammatory myopathy. AJR Am J Roentgenol 2012;198:W475–81. 2013;23:1044–55. 20 Pinal-Fernandez I, Casal-Dominguez M, Carrino JA, et al. Thigh muscle MRI in 9 Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med immune-mediated necrotising myopathy: extensive oedema, early muscle damage 1975;292:344–7. and role of anti-SRP autoantibodies as a marker of severity. Ann Rheum Dis 10 Bohan A, Peter JB. Polymyositis and dermatomyositis (second of two parts). N Engl J 2017;76:681–7. Med 1975;292:403–7. 21 Maetzler W, Reimold M, Schittenhelm J, et al. Increased [11C]PIB-PET levels in 11 lundberg IE, Miller FW, Tjärnlund A, et al. Diagnosis and classification of idiopathic inclusion body myositis are indicative of deposition. J Neurol Neurosurg inflammatory myopathies. J Intern Med 2016;280:39–51. Psychiatry 2011;82:1060–2. http://ard.bmj.com/ on September 29, 2021 by guest. Protected copyright.

662 Lilleker JB, et al. Ann Rheum Dis 2019;78:657–662. doi:10.1136/annrheumdis-2018-214644